Core B - Small Molecule Screening The Laboratory for Drug Discovery in Neurodegeneration (LDDN) was established in late 2001 to collaborate with the Harvard Medical School neuroscience community to discover chemical entities that could become the starting points for development into a new generation of drugs to treat neurodegenerative diseases. The LDDN has developed resources and expertise in assay development, automation, high-throughput screening, and medicinal chemistry. During its three years of operation, the LDDN has established a track record of success, working on no less than twenty-five screening projects and launching half-a-dozen medicinal chemistry projects based on hits discovered in these projects. As a Core of the proposed HD Center Without Walls , the LDDN will provide the following services to Center participants: (i) consult on all aspects of assay development, (ii)transfer assay methodology from participant's laboratory to the LDDN, (iii) miniaturize and automate assays, (iv) screen automated assay against LDDN's 100Klibrary of drug-like compounds, (v) identify authentic screening hits and eliminate false positives, and (vi)consult on best path forward, including choice of secondary screens, appropriate mechanism of action studies, and potential of hits for medicinal chemical optimization